A human C-type retrovirus has been found to be associated with certain adult T-cell malignancies. Lymphocytes from these patients were established in long-term tissue culture using the human T-cell growth factor. Studies were carried out to examine the cell surface markers of cells infected and with producing the human T-cell lymphoma virus (HTLV). HLA typing was performed on these cells. The virus was transferred to human umbilical cord blood lymphocytes by coculture. Cytotoxic lymphocytes were developed against an autologous cell line established from one of the patients. Cell lines established from patients with the adult T-cell leukemias and lymphomas expressed more than the expected two alloantigens controlled by the HLA-A or HLA-A locus. Alloantisera detecting these altered determinants were confined to the HLA-AW19 cross-reactive group and the HLA-B5 cross-reactive group. A monoclonal antibody detecting a polymorphic epitope on HLA alloantigens of these two cross-reactive groups was developed by Dr. Bart Haynes. This monoclonal antibody was found to react with all cells infected with HTLV and producing products of this virus. Human umbilical cord lymphocytes infected with the virus by coculture also expressed altered HLA alloantigenic determinants. These alterations mirrored those seen with tumor cell lines established from patients. Thus, the appearance of neoantigens suggests an association of HTLV provirus replication and HLA alloantigenic expression. Cell surface markers were examined on cell lines established from patients and cell lines established by coculturing with the human T-cell lymphoma virus. These cells were predominantly OKT4+ (helper phenotype). These cells also expressed increased HLA-DR and an antigen detected by the Tac antibody which detects the receptor for T-cell growth factor. A cytotoxic T-cell line, established from a patient with the HTLV-associated disease, killed autologous cells and another cell line, but was not cytotoxic for other cell lines established from patients with HTLV. The cytotoxicity appeared to be genetically restricted by HLA determinants B8 and DR3.